Ca2+-binding protein 2 inhibits Ca2+-channel inactivation in mouse inner hair cells

2017-02-28 | journal article

Jump to:Cite & Linked | Documents & Media | Details | Version history

Cite this publication

​Ca2+-binding protein 2 inhibits Ca2+-channel inactivation in mouse inner hair cells​
Picher, M. M. ; Gehrt, A. ; Meese, S. ; Ivanovic, A. ; Predoehl, F. ; Jung, S.   & Schrauwen, I. et al.​ (2017) 
Proceedings of the National Academy of Sciences of the United States of America114(9) pp. E1717​-E1726​.​ DOI: https://doi.org/10.1073/pnas.1617533114 

Documents & Media

License

GRO License GRO License

Details

Authors
Picher, Maria Magdalena ; Gehrt, Anna ; Meese, Sandra ; Ivanovic, Aleksandra ; Predoehl, Friederike ; Jung, SangYong ; Schrauwen, Isabelle; Dragonetti, Alberto Giulio; Colombo, Roberto; Van Camp, Guy; Strenzke, Nicola ; Moser, Tobias 
Abstract
Ca2+-binding protein 2 (CaBP2) inhibits the inactivation of heterologously expressed voltage-gated Ca2+ channels of type 1.3 (CaV1.3) and is defective in human autosomal-recessive deafness 93 (DFNB93). Here, we report a newly identified mutation in CABP2 that causes a moderate hearing impairment likely via nonsense-mediated decay of CABP2-mRNA. To study the mechanism of hearing impairment resulting from CABP2 loss of function, we disrupted Cabp2 in mice (Cabp2LacZ/LacZ ). CaBP2 was expressed by cochlear hair cells, preferentially in inner hair cells (IHCs), and was lacking from the postsynaptic spiral ganglion neurons (SGNs). Cabp2LacZ/LacZ mice displayed intact cochlear amplification but impaired auditory brainstem responses. Patch-clamp recordings from Cabp2LacZ/LacZ IHCs revealed enhanced Ca2+-channel inactivation. The voltage dependence of activation and the number of Ca2+ channels appeared normal in Cabp2LacZ/LacZ mice, as were ribbon synapse counts. Recordings from single SGNs showed reduced spontaneous and sound-evoked firing rates. We propose that CaBP2 inhibits CaV1.3 Ca2+-channel inactivation, and thus sustains the availability of CaV1.3 Ca2+ channels for synaptic sound encoding. Therefore, we conclude that human deafness DFNB93 is an auditory synaptopathy.
Issue Date
28-February-2017
Journal
Proceedings of the National Academy of Sciences of the United States of America 
eISSN
1091-6490
Language
English

Reference

Citations


Social Media